Arévalo J C, Wu S H
Skirball Institute of Biomolecular Medicine Lab 5-14, NYU School of Medicine, 540 First Avenue, New York, NY, 10016, USA.
Cell Mol Life Sci. 2006 Jul;63(13):1523-37. doi: 10.1007/s00018-006-6010-1.
Neurotrophins are growth factors implicated in the development and maintenance of different neuronal populations in the nervous system. Neurotrophins bind to two sets of receptors, Trk receptor tyrosine kinases and the p75NTR receptor, to activate several different signaling pathways that mediate various biological functions. While Trk receptor activation has been well-studied and triggers the well-characterized Ras/Rap-MAPK, PI3K-Akt, and PLCgamma-PKC cascades, p75NTR signaling is more complex, and its in vivo significance has not yet been completely determined. In the last few years, p75NTR has received much attention mainly due to recent findings describing pro-neurotrophins as new ligands for the receptor and the ability of the receptor to form different complexes with other transmembrane proteins. This review will update the neurotrophin signaling pathways known for Trk receptors to include newly identified Trk-interacting molecules and will address surprising new findings that suggest a role for p75NTR in different receptor complexes and functions.
神经营养因子是一类生长因子，参与神经系统中不同神经元群体的发育和维持。神经营养因子与两组受体结合，即Trk受体酪氨酸激酶和p75NTR受体，以激活几种不同的信号通路，这些信号通路介导各种生物学功能。虽然Trk受体激活已得到充分研究，并触发了特征明确的Ras/Rap-MAPK、PI3K-Akt和PLCγ-PKC级联反应，但p75NTR信号传导更为复杂，其在体内的意义尚未完全确定。在过去几年中，p75NTR受到了广泛关注，主要是由于最近的研究发现前神经营养因子是该受体的新配体，以及该受体与其他跨膜蛋白形成不同复合物的能力。本综述将更新已知的Trk受体神经营养因子信号通路，以纳入新发现的Trk相互作用分子，并探讨一些令人惊讶的新发现，这些发现表明p75NTR在不同的受体复合物和功能中发挥作用。
